纤维化是逐渐导致肾功能损失的进行性肾脏病普遍的病理现象。以往的研究表明CDC20通过调节上皮间充质转化（EMT）和成纤维细胞浸润在癌症中发挥作用，表明CDC20在调节纤维反应中的潜力。然而，CDC20在肾脏纤维化中的作用还不清楚。在此，我们报告在慢性肾脏病（CKD）患者的肾小管上皮细胞和成纤维细胞中表达的肾脏CDC20显著上调，与肾纤维化的严重程度呈正相关。在单侧尿路梗阻小鼠中，CDC20也显著增强，并且与CDC20抑制剂Apcin治疗改善了肾纤维化。一致地，在小鼠近曲小管上皮细胞和大鼠成纤维细胞中药理性抑制CDC20减轻了TGF-β1诱导的纤维反应，而CDC20过表达加剧了这种反应。进一步的研究表明，CDC20诱导β-连接蛋白的核转运，从而启动和促进CKD的病理过程。因此，肾小管细胞和成纤维细胞中增强的CDC20通过激活β-连接蛋白促进肾脏纤维化，而CDC20的抑制可能作为预防和治疗肾脏纤维化的一种有希望的策略。版权所有© 2023 Elsevier B.V.。保留所有权利。

Fibrosis is a common pathological phenomenon in progressive kidney disease leading to eventual loss of kidney function. Previous studies demonstrated that CDC20 plays a role in cancers by regulating epithelial-mesenchymal transition (EMT) and the infiltration of fibroblasts, suggesting the potential of CDC20 in regulating fibrotic response. However, the role of CDC20 in renal fibrosis is yet unclear. Herein, we reported that renal CDC20 was remarkably upregulated in renal tubular epithelial cells and fibroblasts in chronic kidney disease (CKD) patients, which was in line with a positive correlation with the severity of kidney fibrosis. In mice with unilateral urinary obstruction, CDC20 was also strikingly enhanced, and treatment with Apcin, an inhibitor of CDC20, ameliorated kidney fibrosis. Consistently, the pharmacological inhibition of CDC20 in mouse proximal tubular epithelial cells and rat fibroblasts attenuated TGF-β1-induced fibrotic responses, while overexpression of CDC20 aggravated such responses. Additional studies revealed that CDC20 induces nuclear translocation of β-catenin, which in turn initiates and promotes the pathological process of fibrosis in CKD. Thus, enhanced CDC20 in renal tubular cells and fibroblasts promotes renal fibrosis by activating β-catenin, and CDC20 inhibition may serve as a promising strategy for the prevention and treatment of renal fibrosis.Copyright © 2023 Elsevier B.V. All rights reserved.